Presently available data suggest a relationship between lifelong exposure to enteric antigens from microbial and dietary origin, and the development and subsequent decline of immune potential. In an effort to quantitate this relationship, male germfree C3H HeCr mice will be exposed to three different levels of enteric antigenicity. (a) Maintenance on ultra-filtered low molecular weight diet in an antigen-free environment, (b) maintenance on radiation-sterilized natural-type solid diet, and (c) conditions under (b), but with addition of 1 mg endotoxin/kg diet to simulate the immune-stimulating effect of gram-negative microorganisms. To determine if antigenic stimulation during early life is of critical importance for full development of immune potential, and to determine if rapid maturation per se affects the rate of immune decline, part of the mice in group (c) will be shifted to (a) maintenance at 3 months of age. Humoral and cellular immune function will be evaluated at 3, 8-10 and 18-20 months and related to aspects of general function such as metabolic rate, regional blood flow, enzyme inducibility, etc. Results will be compared with data obtained from similar mice harboring a non-pathogenic conventional microflora. The data should indicate how much the elements of lifelong antigenic exposure inherent to a conventional ecosystem contribute to development and decline of immune potential.